Anti-Angiogenesis by a Novel VEGF-Intrakine Strategy for Breast Cancer Therapy
Abstract
Angiogenesis plays a pivotal role in tumor growth and metastasis. VEGF, an endothelial specific mitogen and an angiogenesis inducer in vivo, is one of the most important tumor angiogenesis growth factor. KDR, a VEGF receptor, appears to be the major transducer of VEGF signals in endothelial cells. A tethered intracellular antibody ("intrabody") strategy has been used successfully for both phenotypic and functional knockouts of target molecules. In this study, we have targeted a KDR single chain antibody (scFv) p3S5 to the endoplasmic reticulum (ER) using a c-terminal endoplasmic retention signal (KDEL). We hypothesized that the tethered KDR intrabody would bind newly synthesized KDR and block its transport to the surface of endothelial cells, thereby inhibiting VEGF-induced proliferation. The tethered intrabody significantly reduced KDR expression (from 82.5 % 12.5% to 27.9 + 13.6%, P <0.005) in successfully transfected cells. These results demonstrate the potential for using an intrabody strategy to block angiogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396346
Entities
People
- David Sane
- Yurong Y. Wheeler
Organizations
- Wake Forest University